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Completed

NCT Number: NCT00987935

A Phase I / II Trial of Nintedanib in Asian Hepatocellular Carcinoma Patients

This study is to evaluate the safety, appropriate dose, and efficacy of BIBF 1120 in liver cancer patients

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Key information

Conditions

Carcinoma, Hepatocellular Adenocarcinoma Carcinoma Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

1199.39.82001 Boehringer Ingelheim Investigational Site, Seoul, South Korea

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Hepatocellular carcinoma, either histologically/cytologically confirmed or clinically diagnosed, which is not amenable to curative surgery or loco-regional therapy
  • Age 18 years or older
  • Eastern Cooperative Group performance score of 2 or less
  • Child-Pugh score of 7 or less
  • Written informed consent in accordance with International Conference on Harmonisation (ICH) and Good Clinical Practice (GCP) and local legislation

Exclusion criteria

  • Prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase II)
  • More than one line of prior systemic therapy for metastatic/unresectable hepatocellular carcinoma (for phase I)
  • Uncontrolled or refractory ascites to adequate medical therapy
  • Bilirubin greater than 1.5 times upper limit of normal
  • Aspartate amino transferase or alanine amino transferase greater than 5 times upper limit of normal
  • Absolute neutrophil count less than 1500/microliter
  • Platelet count less than 75000/microliter
  • Hemoglobin less than 9 g/dL
  • Serum creatinine greater than 1.5 times upper limit of normal

Treatment and study plan

Sorafenib

Drug

400 mg twice daily

BIBF 1120

Drug

Twice daily

Primary outcomes

  1. Maximum Tolerated Dose in Phase I

    Time frame: 4 weeks

    The MTD was defined as the highest dose studied for which the incidence of DLTs was 0/3 or less than 2/6 patients during the first treatment course.

  2. Time to Progression (TTP) in Phase II

    Time frame: From randomization until data cut-off (28 Sep 2012); Up to 77 weeks

    TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.

Secondary outcomes

  1. Time to Progression (TTP) in Phase II (Follow-up Analyses)

    Time frame: From randomization until disease progression or data cut-off (16 Jul 2014); Up to 171 weeks

    TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.

  2. Incidence and Intensity of Adverse Events (AEs) Reported as the Number of Patients With AEs According to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Throughout the Treatment Period.

    Time frame: AEs with an onset during therapy with study treatment or within 28 days after discontinuation of study treatment (up to 1066 days)

    Incidence and worst intensity (severity) of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).

  3. Incidence of Dose Limiting Toxicity in Phase I

    Time frame: 4 weeks

    Number of patients with dose limiting toxicity are presented

  4. Objective Tumour Response by RECIST

    Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks

    Objective RECIST 1.0 tumour response was defined as Complete Response (CR) or Partial Response (PR) and was derived from the patient's best objective RECIST 1.0 response based on central independent review.

    95% Confidence Interval presented below are computed by Clopper and Pearson method.

  5. Progression Free Survival (PFS)

    Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks

    PFS by RECIST 1.0 was defined as the duration from date of randomisation to date of progression or death, whichever occurred earlier, based on central independent review.

  6. Overall Survival

    Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks

    Overall survival was defined as the duration from date of randomisation to the date of death.

  7. AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of Nintedanib

    Time frame: Day1, Day15 and Day 16

    AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of Nintedanib

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

  8. AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 (Metabolite of Nintedanib)

    Time frame: Day1, Day15 and Day 16

    AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of BIBF 1202 (metabolite of Nintedanib).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

  9. AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 Glucuronide (Metabolite of Nintedanib)

    Time frame: Day1, Day15 and Day 16

    AUC0-12,ss,norm of BIBF 1202 glucuronide (Metabolite of Nintedanib):

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

  10. Cmax,ss,Norm (Maximum Concentration of the Nintedanib in Plasma at Steady State, Normalised Values)

    Time frame: Day1, Day15 and Day 16

    Cmax,ss,norm (maximum concentration of the Nintedanib in plasma at steady state, normalised values).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

  11. Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 in Plasma at Steady State, Normalised Values)

    Time frame: Day1, Day15 and Day 16

    Cmax,ss,norm (maximum concentration of the BIBF 1202 in plasma at steady state, normalised values).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

  12. Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 Glucuronide in Plasma at Steady State, Normalised Values)

    Time frame: Day1, Day15 and Day 16

    Cmax,ss,norm (maximum concentration of the BIBF 1202 glucuronide in plasma at steady state, normalised values).

    Detailed time points of sampling are:

    Phase I and selected phase II patients in the Nintedanib arm:

    Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

  13. fe0-12,ss (Fraction Excreted in Urine Between 0 and 12 Hours at Steady State) for Nintedanib

    Time frame: 0 to 4 hours (h), 4 to 12 h, and 12 to 24 h after nintedanib

    fe0-12,ss (fraction excreted in urine between 0 and 12 hours at steady state) for Nintedanib.

    The reported value corresponds to the percentage of administered dose.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

A Multicenter, Open Label, Phase I/Randomized II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Sorafenib for Advanced Hepatocellular Carcinoma Patients in Asia.

Important dates

Study start
2009
Primary completion
2014
Study completion
2016
First posted
Oct 1, 2009
Registry last updated
Mar 10, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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